Helicobacter pylori (H. Pylori) is a gram-negative spiral organism which is found overlying the gastric epithelium in approximately 50% of adults in this country. We and others have confirmed a causal relationship between H. pylori infection and gastritis and peptic ulcer disease. Recently this infection has been implicated in the pathogenesis of gastric cancer. Although in-vitro studies indicate H. pylori is sensitive to most antimicrobial agents, numerous studies including our own have demonstrated the difficulty in consistently eradicating H. pylori from the gastric epithelium. Therefore, prevention of infections by oral immunization is an alternative approach for control of disease. Among several existing animal models for H. pylori-associated gastritis, a germ-free mouse model in our laboratory. Our preliminary results have shown that an oral vaccine containing Helicobacter antigens results in significantly elevated levels of anti-Helicobacter IgA antibodies in gastric secretions thereby conferring protection from infection. We have also shown that passive administration of anti-Helicobacter antibody can also prevent acute Helicobacter infection. There are a number of unanswered questions, however, which are the focus of this proposal. We seek to optimize our oral vaccine protocol for induction of protection from Helicobacter infection. A second area of concern is the possibility that the anti-Helicobacter immune response in addition to preventing infection could also play a role in the development of the gastric inflammation associated with Helicobacter infection. We plan a series of experiments to investigate this. Gastric tissue from immunized, and infected animals will be assessed for the presence of gastritis and immunophenotype for the presence of T cell subsets. Passive transfer of antibodies from infected or immunized mice into naive animals will allow us to determine if antibodies contribute to the pathogenesis of gastritis. If we are able to demonstrate infection, we will attempt to distinguish the disease producing antigens from protective ones. These studies may ultimately allow us to develop a safe efficacious subunit vaccine to prevent the morbidity and potential long-term consequences of Helicobacter infection.